Field of the Invention
The present disclosure relates to the medical field. More particularly, the disclosed invention relates to the use of a desmoglein 2-derived peptide for treating angiogenesis-related diseases.
Description of Related Art
Angiogenesis is the formation of new capillaries from pre-existing blood vessels. It is a sophisticated process, regulated by the balance between endogenous, pro-angiogenic (or stimulatory) and anti-angiogenic (or inhibitory) factors. A number of pro-angiogenic factors have been identified, non-exclusive examples of which include basic fibroblast growth factor (bFGF), interleukin 1 (IL-1), IL-4, IL-6, IL-8, vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGFb1), matrix metalloproteinase-2 (MMP-2), MMP-9, epidermal growth factor (EGF), tumor necrosis factor (TNF), myeloid growth factor (MGF), angiogenin, angiotropin, plasminogen activator, proteases, hepatocyte growth factor, insulin-like growth factor, prostaglandin E, hypoxaemia, and macrophages derived P factor. Exemplary anti-angiogenic factors include, interferons, thrombospondin, angiostatin, endostatin, IL-10, IL-12, platelet-derived factor, vascular endothelial growth inhibitor (VEGI), tissue matrix metalloproteinase inhibitors (MMPI), and plasminogen activator inhibitor.
Upon the activation by one or more pro-angiogenic factor or by the pro-angiogenic signal(s) derived therefrom, endothelial cells resting in the parent vessels synthesize and release degrading enzymes allowing the endothelial cells to migrate, proliferate and finally differentiate to give rise to blood vessels. Physiological angiogenesis normally takes place during embryonic and fetal organogenesis, reproductive cycle (e.g., female menstrual cycle), repair processes, wound healing processes and tissue regeneration. However, in many pathological conditions, the disease appears to be associated with upregulated angiogenesis.
The diseases associated with upregulated or abnormal angiogenesis include: (1) ocular neovascular disease (such as, retinal neovascular disease, neovascular age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity), a disease characterized by invasion of new blood vessels into the retina or cornea, leading to irreversible visual impermanent; (2) rheumatoid arthritis and osteoarthritis; the cells within subchondral spaces and vascular channels, and the chondrocytes secrete various growth factor that induce angiogenesis, which may result in the pathogenesis of synovitis and the subsequent destruction of the articular cartilage; (3) inflammation and inflammatory disease; during inflammation, the inflammatory cytokines (such as cyclooxygenase 2, prostaglandin E2, and thromboxane A2), the inflammatory cells (such as macrophage, T cell, and mast cell), and the hypoxia-inducible factor (HIF) elicit the expression of pro-angiogenic factors that cause angiogenesis; the newly formed vasculature in turn enhance the infiltration of the inflammatory cells, which further deteriorate the inflammation; (4) hereditary diseases, such as Osler-Weber-Rendu disease or hereditary hemorrhagic telangiectasia, are related to the disorder of angiogenesis, in which a multisystemic angiodysplasia is responsible for severe hemorrhage; and (5) tumor formation and metastasis; tumor cells secret various pro-angiogenic factors that promote the formation of new blood vessels via angiogenesis process; the new blood vessels are important in tumor growth by providing tumor cells adequate nutrients and oxygen, and are correlated with tumor metastasis by providing a route for tumor migration and invasion.
In view of the foregoing, there exists a need in the art for providing novel medicaments and methods capable of inhibiting angiogenesis and/or treating angiogenesis-related diseases.